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In terms of energy metabolism reprogramming, the deletion of Pde3a and Pde3b inhibits mitochondrial oxidative phosphorylation and promotes glycolysis in PASMCs by downregulating the AMPK/CREB signal and upregulating PDK1/2/4

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How often it happens The rates vary by trial and population: 2,3 TRIUMPH-4 (obesity with knee osteoarthritis): 8.8% on 9 mg, 20.9% on 12 mg, 0.7% on placebo TRANSCEND-T2D-1 (type 2 diabetes): 4.5% on 4 mg, 2.3% on 9 mg, 4.4% on 12 mg, 0% on placebo Phase 2 trial (Jastreboff 2023): not reported The TRIUMPH-4 numbers are markedly higher than those of TRANSCEND-T2D-1

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